Indication

IXEMPRA is indicated in combination with capecitabine for the treatment of patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated.

Think IXEMPRA® (ixabepilone) when resistance emerges in mBC1

When resistance emerges in the adjuvant setting1

Consider IXEMPRA + capecitabine in patients resistant to an anthracycline (progressing while on therapy or within 6 months) and a taxane (progressing while on therapy or within 12 months)

When resistance emerges in the metastatic setting1

Consider IXEMPRA + capecitabine in patients who are resistant to an anthracycline (progressing within 3 months) or in whom further anthracycline use is contraindicated and who progress within 4 months of taxane therapy

Consider IXEMPRA as monotherapy in patients resistant or refractory to an anthracycline, a taxane, and capecitabine

IXEMPRA, in combination with capecitabine, is the only FDA-approved, non-taxane microtubule-targeting agent indicated as first-line therapy for the treatment of patients with metastatic or locally advanced breast cancer resistant to an anthracycline and a taxane1,2

Dose adjustment for toxicities*

Re-treatment criteria1

Dose adjustments at the start of a cycle should be based on nonhematologic toxicity or blood cell counts from the preceding cycle following the guidelines in the “Dose adjustment for toxicities” table above

Patients should not begin a new cycle of treatment unless the neutrophil count is ≥1,500 cells/mm3, the platelet count is ≥100,000 cells/mm3, and nonhematologic toxicities have improved to grade 1 (mild) or resolved

Dose modification for patients with hepatic impairment1

Assessment of hepatic function is recommended before initiation of IXEMPRA and periodically thereafter

Patients with baseline AST or ALT >2.5 × ULN or bilirubin >1.5 × ULN experienced greater toxicity than patients with baseline AST or ALT ≤2.5 × ULN or bilirubin ≤1.5 × ULN when treated with IXEMPRA at 40 mg/m2 in combination with capecitabine or as monotherapy in breast cancer studies

For combination therapy

IXEMPRA in combination with capecitabine is contraindicated in patients with AST or ALT >2.5 × ULN or bilirubin >1 × ULN

For monotherapy

Patients with hepatic impairment should be dosed with IXEMPRA based on the table below

Patients with moderate hepatic impairment should be started at 20 mg/m2; the dosage in subsequent cycles may be escalated up to, but should not exceed, 30 mg/m2 if tolerated

Use in patients with AST or ALT >10 × ULN or bilirubin >3 × ULN is not recommended

Limited data are available for patients with AST or ALT >5 × ULN; caution should be used when treating these patients

Dose adjustments for IXEMPRA monotherapy in patients with hepatic impairment

ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal.
* Excluding patients whose total bilirubin is elevated due to Gilbert syndrome.† Dosage recommendations are for first course of therapy; further decreases in subsequent courses should be based on individual tolerance.

Grapefruit juice may also increase plasma concentrations of IXEMPRA and should be avoided

Based on pharmacokinetic studies, if a strong CYP3A4 inhibitor must be coadministered, a dose reduction to 20 mg/m2 is predicted to adjust the IXEMPRA AUC to the range observed without inhibitors and should be considered

If the strong inhibitor is discontinued, a washout period of approximately 1 week should be allowed before the IXEMPRA dose is adjusted upward to the indicated dose

Toxicity-related deaths occurred in 2 of 43 patients (4.7%) ≥65 years of age with normal baseline hepatic function or mild impairment

Thirty-two of 240 breast cancer patients treated with IXEMPRA as monotherapy were ≥65 years of age, and 6 patients were ≥75 years of age; no overall differences in safety were observed in these patients compared to those <65 years of age

Renal impairment

IXEMPRA is minimally excreted via the kidney

No controlled pharmacokinetic studies were conducted with IXEMPRA in patients with renal impairment

IXEMPRA in combination with capecitabine has not been evaluated in patients with calculated creatinine clearance of <50 mL/min

IXEMPRA as monotherapy has not been evaluated in patients with creatinine >1.5 × ULN

In a population pharmacokinetic analysis of IXEMPRA as monotherapy, there was no meaningful effect of mild or moderate renal insufficiency (CrCl >30 mL/min) on the pharmacokinetics of IXEMPRA

Pregnant women and nursing mothers

Pregnancy Category D: IXEMPRA may cause fetal harm when administered to pregnant women. There are no adequate and well-controlled studies with IXEMPRA in pregnant women. Women should be advised not to become pregnant when taking IXEMPRA. If this drug is used during pregnancy or the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus

It is not known whether IXEMPRA is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from IXEMPRA, a decision must be made whether to discontinue nursing or to discontinue IXEMPRA, taking into account the importance of the drug to the mother

Pediatric use

The safety and effectiveness of IXEMPRA in pediatric patients have not been established

Professional information materials

Nurse's guide to IXEMPRA therapy

This practical guide includes dosing calculations for preparing IXEMPRA® (ixabepilone) for infusion, a review of indications/contraindications, and tables that summarize dose modifications for toxicities and special populations.

Dosing and administration guide

Pharmacy fact sheet

For a reference for how IXEMPRA is supplied (the 15-mg and 45-mg IXEMPRA Kits), use this pharmacy fact sheet, which includes recommended dosing, premedication, and dose modifications for toxicities and special populations.

Study 046: Combination therapy

Ixabepilone Plus Capecitabine for Metastatic Breast Cancer Progressing After Anthracycline and Taxane Treatment. Portions of this journal article may contain information not included in the approved IXEMPRA labeling.

Study 081: Monotherapy

Efficacy and Safety of Ixabepilone (BMS-247550) in a Phase II Study of Patients With Advanced Breast Cancer Resistant to an Anthracycline, a Taxane, and Capecitabine. Portions of this journal article may contain information not included in the approved IXEMPRA labeling.

IXEMPRA monotherapy speaker program deck

Resources for use with patients

Patient brochure

This brochure explains to patients what to expect while being treated with IXEMPRA. This resource lists the indications for IXEMPRA and describes the signs and symptoms of common side effects and the more serious adverse reactions, including peripheral neuropathy, neutropenia, and hypersensitivity.

For reimbursement support, contact R-Pharm US Access and Support in one of the following ways:

R-Pharm US Access and Support enrollment form

Complete this form to enroll your patients in the R-Pharm US Access and Support program. Select from the program’s various services and assistance offerings, including benefits investigation, support with prior authorization, co-pay assistance, and more.

R-Pharm US Access and Support patient authorization form

Patients should complete this form to authorize services and assistance from the R-Pharm US Access and Support program. This form is to be used only when an R-Pharm US Access and Support enrollment form was previously submitted without a patient authorization and agreement signature.

The information provided is intended for use by individuals involved with reimbursement support.

The accurate completion of reimbursement or coverage-related documentation is the responsibility of the healthcare provider and patient. R-Pharm US and its agents make no guarantee regarding reimbursement for any service or item.

Indication

IXEMPRA is indicated in combination with capecitabine for the treatment of patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated.

Indications

IXEMPRA® (ixabepilone) is indicated in combination with capecitabine for the treatment of patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated.

Anthracycline resistance is defined as progression while on therapy or within 6 months in the adjuvant setting or 3 months in the metastatic setting

Taxane resistance is defined as progression while on therapy or within 12 months in the adjuvant setting or 4 months in the metastatic setting

IXEMPRA is indicated as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine.

Important Safety InformationWARNING: Toxicity in hepatic impairment

IXEMPRA® (ixabepilone) in combination with capecitabine is contraindicated in patients with AST or ALT >2.5 × ULN or bilirubin >1 × ULN due to increased risk of toxicity and neutropenia-related death

Caution should be used when using IXEMPRA as monotherapy in patients with AST or ALT >5 × ULN. Use of IXEMPRA in patients with AST or ALT >10 × ULN or bilirubin >3 × ULN is not recommended

With monotherapy, grade 4 neutropenia, febrile neutropenia, and serious adverse reactions were more frequent in patients with hepatic impairment

Contraindications

IXEMPRA is contraindicated in patients:

with a known history of a severe (CTC grade 3/4) hypersensitivity reaction to agents containing Cremophor® EL or its derivatives such as polyoxyethylated castor oil

who have a baseline neutrophil count <1500 cells/mm3 or a platelet count <100,000 cells/mm3

Peripheral neuropathy

Peripheral neuropathy was common. Patients treated with IXEMPRA should be monitored for symptoms of neuropathy, such as burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, or neuropathic pain

Neuropathy occurred early during treatment; ~75% of new onset or worsening neuropathy occurred during the first 3 cycles. Patients experiencing new or worsening peripheral neuropathy may require changes in the dose or discontinuation of IXEMPRA

Neuropathy was the most frequent cause of treatment discontinuation due to drug toxicity. Caution should be used when treating patients with diabetes mellitus or preexisting peripheral neuropathy

Myelosuppression

Myelosuppression is dose-dependent and primarily manifested as neutropenia

Patients should be monitored for myelosuppression; frequent peripheral blood cell counts are recommended for all patients receiving IXEMPRA

Patients who experience severe neutropenia or thrombocytopenia should have their dose reduced. Neutropenia-related deaths occurred in 1.9% of 414 patients with normal hepatic function or mild hepatic impairment treated with IXEMPRA in combination with capecitabine. Neutropenia-related death occurred in 0.4% of 240 patients with IXEMPRA as monotherapy

Hypersensitivity reaction

Premedicate with an H1 and an H2 antagonist approximately 1 hour before IXEMPRA infusion and observe for hypersensitivity reactions (eg, flushing, rash, dyspnea, and bronchospasm)

In case of severe hypersensitivity reactions, infusion of IXEMPRA should be stopped and aggressive supportive treatment (eg, epinephrine, corticosteroids) started

Patients who experience a hypersensitivity reaction in one cycle of IXEMPRA must be premedicated in subsequent cycles with a corticosteroid in addition to the H1 and H2 antagonists, and extension of the infusion time should be considered

Pregnancy

Women should be advised not to become pregnant when taking IXEMPRA. If this drug is used during pregnancy or the patient becomes pregnant, the patient should be apprised of the potential hazard to the fetus

Cardiac adverse reactions

Caution should be exercised in patients with a history of cardiac disease. Discontinuation of IXEMPRA should be considered in patients who develop cardiac ischemia or impaired cardiac function due to reports of cardiovascular adverse reactions (eg, myocardial ischemia, supraventricular arrhythmia, and ventricular dysfunction). The frequency of cardiac adverse reactions (myocardial ischemia and ventricular dysfunction) was higher in the IXEMPRA in combination with capecitabine (1.9%) than in the capecitabine alone (0.3%) treatment group

Potential for cognitive impairment from excipients

IXEMPRA contains dehydrated alcohol USP. Consideration should be given to the possibility of central nervous system and other effects of alcohol

Indications

IXEMPRA® (ixabepilone) is indicated in combination with capecitabine for the treatment of patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated.

Anthracycline resistance is defined as progression while on therapy or within 6 months in the adjuvant setting or 3 months in the metastatic setting

Taxane resistance is defined as progression while on therapy or within 12 months in the adjuvant setting or 4 months in the metastatic setting

IXEMPRA is indicated as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine.